1 Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
2 Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Otolaryngol Head Neck Surg. 2018 Jan;158(1):110-117. doi: 10.1177/0194599817730304. Epub 2017 Sep 12.
Objective To evaluate the adverse effects and therapeutic efficacy of our biocompatible polymer platform delivering targeted local therapy of cytokine CCL21 and cisplatin in a partially resected xenograft animal model of head and neck squamous cell carcinoma. In addition, to evaluate the efficacy of cotreatment with radiotherapy and assess the biocompatibility of the cisplatin-eluting polymer in the murine neck. Study Design Experimental animal study. Setting Academic research laboratory. Subjects and Methods SCCVII/SF cell injection established head and neck squamous cell carcinoma tumors in C3H/HeJ mice. Subjects underwent surgery, and a chemokine-eluting polymer was implanted into the resected site. Subjects treated with cisplatin received radiation or no radiation, and tissue was harvested after 8 weeks to assess polymer biocompatibility. Results Our results with the polymer platform significantly ( P < .05) reduced SCCVII/SF tumor size in C3H/HeJ mice with cisplatin (49% ± 8.7%, Δ3.4 ± 0.6 cm [95% CI]), CCL21 (42% ± 4.8%, Δ3.5 ± 0.4 cm), and cisplatin/CCL21 dual-agent polymer (82% ± 4.4%, Δ8.0 ± 0.4 cm) as compared with controls. Cisplatin polymer with high-dose (16 Gy) and low-dose (4 Gy) radiation reduced tumor mass (respectively, 92% ± 7.2%, Δ6.1 ± 0.5 cm; 85% ± 7.4%, Δ5.7 ± 0.5 cm) as compared with the reduction from high-dose radiotherapy alone (70% ± 7.9%, Δ4.7 ± 0.5 cm). No significant toxicity or inflammation was noted on histopathology after radiotherapy and cisplatin-eluting polymer treatment. Conclusion Cisplatin, CCL21, and cisplatin/CCL21 dual-agent polymer all exhibit significant antitumor effects and decrease tumor burden. Moreover, combination cisplatin polymer with radiotherapy may permit a decrease in intensity of radiation therapy in patients having received the cisplatin polymer. Histopathologic analysis suggests that the polymer is free from significant adverse effects in this model and warrants clinical trial.
目的 评估我们的生物相容聚合物平台在头颈部鳞状细胞癌的部分切除异种移植动物模型中靶向局部递送细胞因子 CCL21 和顺铂的不良反应和治疗效果。此外，评估放射治疗的辅助治疗效果，并评估顺铂洗脱聚合物在小鼠颈部的生物相容性。 研究设计 实验动物研究。 研究机构 学术研究实验室。 研究对象和方法 通过 SCCVII/SF 细胞注射在 C3H/HeJ 小鼠中建立头颈部鳞状细胞癌肿瘤。接受手术的研究对象，将趋化因子洗脱聚合物植入切除部位。接受顺铂治疗的研究对象接受或不接受放射治疗，并在 8 周后采集组织以评估聚合物的生物相容性。 结果 我们使用聚合物平台的结果显示，顺铂（49%±8.7%，Δ3.4±0.6cm [95%CI]）、CCL21（42%±4.8%，Δ3.5±0.4cm）和顺铂/CCL21 双药物聚合物（82%±4.4%，Δ8.0±0.4cm）显著（P<0.05）减少了 C3H/HeJ 小鼠的 SCCVII/SF 肿瘤大小，与对照组相比。与单独高剂量（16Gy）和低剂量（4Gy）放射治疗相比，顺铂聚合物（分别为 92%±7.2%，Δ6.1±0.5cm；85%±7.4%，Δ5.7±0.5cm）降低了肿瘤体积，与高剂量放射治疗单独降低（70%±7.9%，Δ4.7±0.5cm）相比。在放射治疗和顺铂洗脱聚合物治疗后，组织病理学未见明显毒性或炎症。 结论 顺铂、CCL21 和顺铂/CCL21 双药物聚合物均表现出显著的抗肿瘤作用，并降低肿瘤负担。此外，顺铂聚合物联合放射治疗可能允许减少接受顺铂聚合物治疗的患者的放射治疗强度。组织病理学分析表明，该聚合物在该模型中无明显不良反应，值得临床试验。
